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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Intestinal drug efflux: formulation and food effects.

The intestine, primarily regarded as an absorptive organ, is also prepared for the elimination of certain organic acids, bases and neutral compounds depending on their affinity to intestinal carrier systems. Several of the transport systems known to mediate efflux in the major clearing organs--liver and kidney--are also expressed in the intestine. Examples of secretory transporters in the intestine are P-glycoprotein, members of the multidrug resistance associated protein family, breast cancer resistance protein, organic cation transporters and members of the organic anion polypeptide family. In this communication, the P-glycoprotein mediated intestinal secretion of talinolol, a model compound showing metabolic stability, has been investigated in the jejunum, ileum and colon of rat intestine by single-pass perfusion. A model has been developed which demonstrates an increase in carrier-mediated secretion in the order jejunum<ileum<colon. Furthermore, the potency of common excipients in peroral drug products towards inhibition of P-gp mediated secretion has been investigated using a radioligand-binding assay and transport studies in Caco-2 cell monolayers. Finally, evidence is provided which demonstrates that constituents of grapefruit juice not only may influence intestinal drug metabolism, but can also interfere with secretory transport systems, leading to a new and yet undescribed mechanism in drug-food interactions.[1]


  1. Intestinal drug efflux: formulation and food effects. Wagner, D., Spahn-Langguth, H., Hanafy, A., Koggel, A., Langguth, P. Adv. Drug Deliv. Rev. (2001) [Pubmed]
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